Surface hybridization is a reaction in which nucleic acid analyte, or “target”, molecules present in solution bind to “probe” strands immobilized on a solid support due to associations between nucleic bases on the probe and target strands. Surface hybridization plays a key role in a number of bioanalytical techniques, including DNA microarrays and sequencing technologies. In diagnostic applications the extent of probe-target association is usually quantified by “labeling” of the target analyte, or of the hybridized probe/target complex, through covalent or physical association with a molecular moiety designed to facilitate detection. Examples of such moieties include fluorophores, radiolabels, chemiluminescent labels, and electrochemically-active labels, resulting in signals based in light (fluorescence, luminescence), radioactivity, or current that can be correlated with the extent of surface hybridization. On the other hand, detection of unlabeled, and thus unaltered, samples can decrease assay costs, simplify preparation of the sample, decrease experimental variability, and avoid possible alteration of the probe-target interaction. For example, use of folded DNA probes such as hairpins, molecular beacons, and surface-quenched beacons can detect unlabeled targets through a change in conformation of the folded probe that results in emission of fluorescence or altered charge transfer characteristics, depending on the type of probe used. In these instances, the requirement is to design a specific probe sequence that folds differently in the absence and presence of the target. While they enable detection of unlabeled samples, a disadvantage of such folded probes is the requirement for a specific conformation in the unhybridized state, which introduces extra design steps, requires optimization of the folding thermodynamics, and results in introduction of additional nucleotides into the probe that can compromise accuracy with which target sequences are recognized.